Effects of intravenous amino acid administration with Y-90 DOTA-Phe1-Tyr3-Octreotide (SMT487[OctreoTher) treatment.

Y-90-DOTA-Phe1-Tyr3-Octreotide (90Y-SMT 487, OctreoTher) has shown potential for effectively treating patients with neuroendocrine tumors. The dose-limiting organ for this agent is the kidney. The purpose of this work is to assess the effectiveness of a commercially available amino acid solution on reducing renal uptake of 90Y-SMT 487 and determine the safety profile of this solution. Subjects with In-111 pentetreotide positive tumors and normal creatinine levels were treated with 3 cycles of 90Y-SMT 487, 120 mCi/cycle, at 6-9 week intervals. During each treatment two liters of an amino acid solution containing arginine and lysine (Aminosyn II 7%, Abbott Laboratories, Abbott Park, IL) were infused IV over 4 hours. Adverse events were recorded. To assess the effect of Aminosyn II on renal uptake of 90Y-SMT 487, a subgroup of subjects underwent bremsstrahlung imaging 24 hours following infusion. Kidney to liver (K/L) count density ratios were generated from the baseline In-111 pentetreotide images (performed without amino acid infusion) and the 90Y bremsstrahlung images. Follow-up creatinine levels were obtained. Thirty-seven subjects received a total of 89 90Y-SMT 487 treatments. The number of amino-acid infusions associated with one or more episodes of emesis was 53 (62%). During 13 (15%) of these infusions, the Aminosyn II rate had to be reduced because of severe nausea and vomiting. Symptomatic flushing occurred during 16 (18%) of the infusions. One subject experienced a near syncopal event shortly after completing the infusion. Creatinine levels remained normal in 34 of 36 subjects during a mean follow-up period of 9.8 months. Fourteen subjects underwent bremsstrahlung imaging following infusion of 90Y-SMT 487. Kidney uptake appeared to decrease with administration of the amino acid solution in 13 of 14 subjects. For the 28 individual kidneys, the mean percent decrease in the Kidney/Liver uptake ratio with the amino acid solution was found to be 32%. We conclude that 2 L of Aminosyn II 7% infused over 4 hours appears to notably reduce renal uptake of 90Y-SMT 487. Aminosyn is generally well tolerated, particularly at lower infusion rates with occasional moderate to severe nausea and vomiting at higher rates.

Gastroenteropancreatic neuroendocrine tumors in children and young adults.

We review the imaging findings of pediatric gastroenteropancreatic neuroendocrine tumors (GEP-NETs) using contemporary anatomic and molecular imaging techniques. A low index of suspicion can result in significant delays in diagnosis of pediatric GEP-NETs. A multimodality imaging approach, using both anatomic and functional imaging, is essential in the diagnosis, staging, and surveillance of these potentially malignant tumors.

The survivin:Fas ratio is predictive of recurrent disease in neuroblastoma.

BACKGROUND/PURPOSE: Several clinical and biologic features of neuroblastoma (NB) are used to predict the risk of recurrent disease. The balance between antiapoptotic and proapoptotic factors within a tumor may affect its ability to survive. Survivin is an antiapoptotic factor expressed in highly proliferative NB, whereas Fas is a proapoptotic factor that portends a favorable prognosis. The authors determined whether the ratio of survivin to Fas (S:F ratio) is predictive of recurrent disease in patients with NB. The authors previously have shown the S:F ratio is predictive of recurrent disease in pediatric renal tumors. METHODS: The authors quantified the levels of 9 different apoptotic mRNA species using Rnase Protection assay (RPA, Riboquant, PharMingen, San Diego, CA). Twenty-eight primary tumor specimens were evaluated from patients with ganglioneuroma (n = 3), ganglioneuroblastoma (n = 2), and neuroblastoma (n = 23) from tumors of all clinical stages obtained at the time of diagnosis. mRNA levels were calculated as a percentage of L32 for each specimen assayed, and positive expression was assumed to be greater than 10% of L32. RESULTS: Survivin was expressed in 90% of tumors that went on to recur and only in 27.7% of those that were cured. The S:F ratio was significantly greater in tumors that went on to recur (n = 10) compared with those from patients that were cured (n = 18) (median S:F ratio, 3.3 v 0.75; P =.0002, Wilcoxon rank-sum test). A cutoff ratio of 2.3 was highly predictive of tumor recurrence irrespective of clinical stage of disease (area under ROC curve = 0.906). Sensitivity was 80% (CI, 44.4% to 97.5%), specificity was 94.4% (CI, 72.7% to 99.9%), positive predictive value was 88.9% (CI, 51.8% to 99.7%), and negative predictive value was 89.5% (66.9% to 98.7%). Twenty-five of 28 (89.3%) tumor ratios were correct in predicting outcome. CONCLUSIONS: The survivin:Fas ratio in primary tumors may be used to predict the risk for recurrent disease in patients with NB. The S:F ratio appears to be a more sensitive predictor of recurrent disease than survivin expression alone. Determining this ratio may not only be helpful in guiding follow-up of patients with NB, but also may aid in stratifying patients for more aggressive therapeutic strategies.